1. Field of the Invention
The present invention relates generally to the field of sample handling and to sample preconcentration. More particularly, this invention relates to a method and device for concentration of samples, such as analyte solutions, on the principle of crystallization.
2. Description of the Prior Art
In order to meet the requirement of current environmental, biochemical and clinical analysis, where more information is needed to be drawn from a small amount of samples, such as blood or a solution containing quite small amount of interesting compounds, suitable devices and methods need to be developed for handling and concentrating these samples. The most widely used methods currently are based on extraction, such as solid phase extraction, solid phase microextraction, and liquid—liquid extraction. There are also other methods which could be used, such as evaporation. There is hardly any method for concentrating sample solutions based on the principle of crystallization.
When a crystalline phase is formed from a fluid phase, the process is commonly called crystallization. Due to the high selectivity by which atoms, ions, and molecules may be built in a crystal lattice, crystallization has been used in industry for producing high purity compounds. With the selected compounds (usually the major component in the liquids, such as water in aqueous solutions and organic solvents in organic solutions) crystallizing out from the liquid and becoming purified, the other compounds (usually the minor components in the liquid, or analytes when they are the compounds of interest) become concentrated in the remaining liquid. Freeze concentration is a process for concentrating aqueous solutions by removing water in the form of ice. Using crystallization to concentrate samples can provide several advantages over other concentration techniques often used in analytical chemistry, such as extraction and evaporation. Compared with methods of extraction, no organic solvent or any other reagents are needed during crystallization, which will reduce the danger of contamination to samples and the cost for disposing toxic reagents. Compared with evaporation, crystallization can be used to concentrate semi-volatile and volatile samples. In addition, crystallization can concentrate analytes in solid samples which can be changed into liquid state under certain conditions, such as heating them to a certain temperature. Few concentration techniques in current analytical chemistry can concentrate solid samples directly. Until now, there are only a few papers available which address concentration and analysis of organic solvents and anions in aqueous solution based on freeze concentration. The process of freeze concentration is usually quite long, generally several hours, and generally requires large sample solutions (at least several mL).
Recently, with the intense pharmaceutical drug discovery efforts, combinatorial chemistry is offering great challenges to analytical chemistry. Combinatorial chemistry is a style of synthesis in which selected building blocks are combined in different ways so as to produce large numbers, or libraries, of new molecular variants much more efficiently than is possible by traditional synthetic approaches (Chem. Rev., March 1997). It has given drug discovery units in pharmaceutical companies a crank with a very long handle, producing in a few days a 50,000-compound library of new molecular structures. Subsequently compounds showing activity of the kind sought and their structures will need determining. In addition, most combinatorial methodologies yield only 0.1 to micromole quantities of product, which are localized on polymer beads, plastic “pins”, or in microtiter plate wells. Thus, very high analytical sensitivities are demanded. The method described in the present invention which can concentrate analytes in small volumes and concentrate hundred or thousand of them simultaneously could be very useful and highly desirable.